Phenyl-piperidino-coumarans



Patented Mar. 18, 1952 UNITED STATES "PATENT OFFICE 2,589,378 PHENYL-PIPERIDI NO- COUMARANS Hans Henecka, Wuppertal-Elberfeld, Germany, assignor to Schenley Laboratories, Inc., New York, N. Y., a corporation of Delaware No Drawing. Application November 17, 1949, Serial No. 128,016. In Germany October 5, 1948 This invention relates to a process for the production of phenyl-piperidino-coumarans.

I have found that derivatives of phenyl-piperidino coumaran of the following general constitution:

The object is accomplished by first converting the acetonyl ether of [3-o-hydroxyphenyl cinnamio acid nitrile (of. my co-pending applica- 8 Claims. (01. zen-294.7)

The invention is further illustrated by the following example:

Example 100 grams of B-o-acetonyloxy-phenyl-cinnamic acid nitrile of the melting point 83-84" C. (ob- 'tainable by alkylating fl-o-hydroxyphenyl-cinnamic acid nitrile with monochloroor bromoacetone) are dissolved in 200 cos. of piperidine.

When two cos. of 20 per cent methyl-alcoholic caustic potash solution are added rearrangement occurs in an exothermic reaction with an increase in temperature up to 60 C. into 2-acetyl- '.3-phenyl-coumaran-3-acetonitrile. After pour ing the piperidine solution into icy-cold dilute sulfuric acid, taking unwith ether and distilling the residue on evaporation of the ether, a highly viscous, light-yellow oil of the boiling point 173 C. under 0.15 mm. pressure is obtained. The yield amounts to 80 per cent of the. theoretical. 40 grams of this coumaran-derivative dis;

* solved in 250 cos. of methanol are hydrogenated tion Ser. No. 128,015 of even date herewith, concerning hydroxyphenyl-cinnamic acid nitriles) into the 2-acetyl-3-phenyl-coumaran-3-acetonitrile by the treatment with a small amount of alkali. 2 acetyl-3-phenyl-coumaran-3-acetonitrile yields 2.3-(2-methyl-piperidino-3'.4)-3- phenyl-coumaran by hydrogenation which is il- 2 nally converted according "to usual methods into N-methyl-piperidimj-com- I the corresponding pound of the above constitution. The following formulae illustrate the new synthesis:

' CsHa mq konon QiHi coon: 6115 --OCH2.CO.CH3

in the presence of ten grams of Raney-nickel'a't" -110" C. and at a Hz-pressure of 100 kg/cmfi.

After separating from the catalyst. and evaporating, the methanol in vacuo an almost colorless sirup is, obtained which on high vacuum distillation yield-s 2.3- (2-methyl-piperdino-3'.4")

'3-phenyl-coumaran as a water-clear, highlyviscous oil of the boiling point 143 C. under 0.05

mm. pressure.

By methylating this pi'peridino compound ac cording to usual methods, for instance, by the reaction with dimethyl sulfate or preferably with formaldehyde/formic acid,' 2.3-(2'.N-dimethylpiperidino3'.4) -3-phenyl-coumaran is obtained as a readily crystallizing compound. Since the new compound contains three asymmetric C- atoms four stereomeric racemic compounds are 'to be expected. These four stereomers are not formed in equal quantity. By recrystallizing the crude-crystals from ether, acetone or methanol the a-compo'und of themelting point 157-158 C;

is first obtained. It is present in the crude crystallizate in an amount of 50 per cent. From the remaining mother solution an oil is obtained irom which the difficulty soluble hydrochloride of. the fl-compound can be isolated by treatment with n-hydrochloric acid; Ithas a melting point 'of 252-254" C. afterrecrystallization from acetone. The free base obtainable therefrom melts at -107 C. The mother solution containing hydrochloric acid yields a mixture of the 'yand t-compound from which the 'y-compound of the melting point 136-138" C.,can be isolated after distilling in high vacuo (boiling point 147 C.

under 0.075 mm. pressure) by recrystallizing from gasoline. From the filtrate a residual crystallizate is finally obtained which has no sharp melting point (between 125 and 132 C.) and represents a mixture of the 'y-compound and the a-compound, the latter compound beingformed in a very small quantity.

In an analogous manner the following products (melting point 109- NCH:

gong

wherein R and R are substituents of the group consisting of hydrogen and lower alkyl groups, 1

the steps that comprise hydrogenating, with gaseous hydrogen under a pressure of the order of about 100 kilograms per square centimeter, at a temperature within the range of about 100 C. to about 110 C., in the presence of a Raney nickel hydrogenation catalyst, a solution, in an inert organic solvent, of a compound represented by the formula:

and recovering from the reaction mixture an intermediate product represented by the formula:

2. In a process for making a chemical compound represented by the formula:

H2 CH7.

NC Ha thev steps that comprise hydrogenating, with gaseous hydrogen under a pressure of the order of, about kilogram per square centimeter, at a temperature within the range of about 100 C. to about C'., in the presence of a Raney nickel hydrogenation catalyst, a solution, in an inert organic solvent, of a compound represented by the formula:

and recovering from the reaction mixture an; intermediate product represented by the formula:

H: CH3

3. In a process for making a chemical compound represented by the formula:

, NCH:

the steps that comprise hydrogenating, with gaseous hydrogen under a pressure of the order of about 100 kilograms per square centimeter, at a temperature within the range of a about 100 c. to about 110 0., m thepresence of a Raney nickel hydrogenation catalyst; a solution, in an inert organic solvent, of a compound represented by the formula:

and recovering from the reaction mixture an intermediate product represented by the formula:

4. The process defined in claim 1 further characterized in that the inert organic solvent is a lower aliphatic alcohol.

" 5. A chemical compound represented by the formula:

a J 0 H1;

IHCHK i1 wherein R and R are substituents chosen from the group consisting of hydrogen and methyl.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Name Date Plati et a1 May 17, 1949 OTHER REFERENCES Barltrop, Jour. Chem. Soc. (London), 1946, pp. 958-963.

Number 

5. A CHEMICAL COMPOUND REPRESENTED BY THE FORMULA: 